Genotypic and phenotypic correlations of DFNB1-related hearing impairment in the Midwestern United States

OBJECTIVE: To determine the genotypic and phenotypic correlations of hearing impairment (HI) in a midwestern US population related to autosomal recessive nonsyndromic hearing loss locus 1 (DFNB1). DESIGN: A retrospective review. SETTING: Tertiary care children's hospital. PATIENTS: A total of 160 consecutive children diagnosed with idiopathic sensorineural hearing loss. MAIN OUTCOME MEASURES: GJB2 genotype and audiometric phenotype. RESULTS: The prevalence of subjects with HI having biallelic GJB2-related mutations was 15.3% (24/157). Of these 24 patients, 9 (38%) were homozygous 35delG, 6 (25%) had other biallelic nonsense mutations, and 9 (38%) had a missense mutation of at least 1 allele. The allelic prevalence of 35delG was 8.6% (27/314) in the study population and 48% (23/48) in the DFNB1 group. The M34T allele mutation was next most prevalent at 2.2% (7/314) in the study population and 10% (5/48) in the DFNB1 group. Severe to profound HI occurred in 59% of DFNB1 subjects. Genotypes with biallelic nonsense mutations had a high risk of severe to profound HI (88%). DFNB1-related HI was usually bilateral, symmetric, nonprogressive, and had flat audiograms. However, asymmetric HI (22%), sloping audiograms (26%), and even borderline-normal hearing in 1 ear was observed, and these were associated with the presence of at least 1 missense mutation. Two novel mutations, K15T and L90V, were identified. A subject presenting to our clinic with severe to profound HI had a 40% risk of biallelic GJB2 mutation. CONCLUSIONS: Our population represents a consecutively enrolled clinic population with sensorineural hearing loss. In our DFNB1-related HI cohort, the 35delG mutation and severe to profound HI rates were lower than previously reported. Our missense mutation and M34T allelic prevalence rates were higher than expected and were associated with a less severe hearing loss. The presence of biallelic nonsense mutations was associated with severe to profound hearing loss in nearly 90% of cases. Mild asymmetric HI and sloping audiograms were more often associated with missense mutations.     

Should the food intake of patients admitted to acute hospital services be routinely supplemented? A randomized placebo controlled trial

BACKGROUND: Many patients admitted to acute hospital services are underweight or harbour vitamin deficiencies. OBJECTIVES: To determine the effect on patient throughput of a policy of routine vitamin supplementation, and of early routine sipfeed supplementation in 'thin' patients (5-10% weight loss or body mass index 18-22). DESIGN: Factorial randomized placebo controlled trial of oral multivitamins from the first day of admission, and, after nutritional screening, of a nutritionally complete sipfeed from the second day in 'thin' patients. SETTING: Acute medical, surgical and orthopaedic hospital services of a London teaching hospital. PARTICIPANTS: 1561 patients admitted as emergencies were included in the vitamin study of which 549 were included in the sipfeed study. MAIN OUTCOME MEASURE: Length of hospital stay (LOS). RESULTS: Offering multivitamins to acute admissions resulted in a mean change (reduction) in LOS of -0.4 days 95% CI (-2-1.2days). The results suggest greater reductions for those discharged after 10 days: mean change=-2.3 days 95% CI (-5.7 to 1.2). Sipfeed supplementation was associated with an increased mean length of stay 2.8 days 95% CI (-0.8-6.3). 18% of acute admissions were classified undernourished on the basis of BMI, MUAC or percent weight loss combined. CONCLUSIONS: No benefit was observed for sipfeed intervention although a small benefit of less than one day is not excluded. Vitamin supplementation may have slight but economically important benefit.     

Measurement of a novel optic disc topographic parameter, ”spikiness”, in glaucoma

Background: Structural changes in the lamina cribrosa have been implicated in the pathogenesis of glaucomatous optic atrophy, but not observed. This paper presents a novel parameter of topographic variability within the optic disc, termed ”spikiness”, which may reflect glaucoma-related changes in the lamina. Methods: Four age-matched groups of normal patients (n=12, mean age 64.8 years) and patients with ocular hypertension (n=14, mean age 63.1), primary open-angle glaucoma (n=11, mean age 70) and low-tension glaucoma (n=15, mean age 66.3) were recruited. Images of normal and glaucomatous eyes from the Heidelberg Retina Tomograph were imported into ERDAS image processing software where the spikiness data (30 consecutive mean surface height values across the base of the optic cup in both the vertical and horizontal meridians) were extracted in a format that facilitated further statistical analysis. Results: Significant differences in topographic variability (spikiness) existed in the vertical (F=3.64, P=0.01) but not the horizontal meridian (F=1.25, P=0.3) through the optic disc. Spikiness was inversely related to Humphrey mean deviation (P<0.05), and cup-disc ratio (P<0.004) and was directly related to nerve fibre layer thickness (P<0.005). Of particular interest was the finding that the spikiness measure was the only optic disc parameter to significantly discriminate low tension glaucoma from primary open angle glaucoma. Conclusion: A new measure of surface variability (topography) at the floor of the optic cup has been described. The new index of spikiness may represent a measurement of lamina cribrosa fragility which has been implicated, but not previously estimated, in glaucomatous eyes. Received: 6 January 2000 Revised: 27 March 2000 Accepted: 30 March 2000     

Multiple-sited (heterotopic) pregnancy after in vitro fertilization and gamete intrafallopian transfer

Pregnancies occurring simultaneously in different body sites (heterotopic pregnancies) are a rare condition thought to occur in 1 of 30,000 spontaneous pregnancies. Individual cases may occur after in vitro fertilization (IVF) or gamete intrafallopian transfer (GIFT). In the past 4 1/2 years, our unit has performed 6,204 IVF/GIFT or pronuclear stage transfer cycles of treatment. Ten such pregnancies proven by surgical, ultrasound, and histological diagnosis have occurred. In the same period 640 IVF, 355 GIFT, and 6 pronuclear stage transfer clinical pregnancies were achieved. This suggests that the incidence of heterotopic pregnancy after assisted reproduction is closer to 1 of 100 pregnancies. Clinicians managing early complications of IVF, GIFT, and/or pronuclear stage transfer pregnancies should be aware of this relatively high incidence of concomitant intrauterine and extrauterine pregnancy.     

Diuretic resistant oedema: nailing the diagnosis.

Introduction Peripheral oedema is a commonly encountered clinical problem.Although it has many causes, its pathophysiology ultimatelyinvolves two processes: altered capillary haemodynamics andrenal salt and water retention. A minority of cases are resistantto diuretic treatment; causes of such resistance include excessivesodium intake, poor diuretic drug absorption, reduced secretionof free diuretic into urine (for example, in nephrotic syndrome,renal failure, and heart failure), and lymphatic obstruction.We present a case of diuretic-resistant oedema associated withpleural and pericardial effusions. Only after extensive ‘negative’     

Drug effects on REM sleep and on endogenous depression

In earlier work REM sleep deprivation (RSD) by arousals improved endogenous depression. This suggested that drugs producing a similar RSD would have antidepressant activity. The arousal RSD was large, persisted for weeks, and was followed by a REM rebound. We call RSD with these properties arousal-type RSD. The present study reviewed literature from 1962 to 1989 on drug REM sleep effects to examine the hypothesis that drugs producing arousal-type RSD improve endogenous depression. The literature reviewed concerned the REM sleep effects of amine precursors, antidepressants, antihistamines, antipsychotics, barbiturates, benzodiazepines, other hypnotics, drugs affecting cholinergic and noradrenergic neurotransmission, ethanol, lithium and narcotics. Four hundred and sixty-eight relevant papers were read and 215 contributed information that could be used in the review. The findings indicated that all drugs producing arousal-type RSD improved endogenous depression. Four drugs that improved endogenous depression did not produce arousal-type RSD.